| Project/Area Number |
18591260
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Nihon University |
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Principal Investigator |
TERUI Tadashi Nihon University, School of Medicine, Professor (30172109)
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| Co-Investigator(Kenkyū-buntansha) |
RA Chisei Nihon University, School of Medicine, Professor (60230851)
HARA Hiroyuki Nihon University, School of Medicine, Associate Professor (70228625)
OKUYAMA Rhuhei Tbhoku University, Graduate School of Medicine, Associate Professor (80292332)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,940,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥540,000)
Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | skin / eosinophilic inflammation / mast cell / animal model |
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| Research Abstract |
Recent studies suggest that mast cell derived-TNF-alpha plays important roles in the development of contact hypersensitivity induced by hapten. Recently, we revealed that Fc epsilon RI beta-chain controls production of proinflammatory cytokines including TNF-alpha from mast cells through function of three tyrosine residues (Y219/Y229/Y225) of its ITAM. In the present study, we investigated the biological functions of mast cells expressing wild-type or mutated β-chain ITAM in development of the contact hypersensitivity employing mast cell "knock-in" mice.
We prepared mast cells harboring wild-type (YYY) or Fc epsilon RI beta-chain ITAM mutant (FFF) by employing a retrovirus-mediated gene transfer into BMMCs derived from Fc epsilon RI beta-chain -/- mice. Those mast cells were intradermally transferred into ears of mast cell deficient mice (W/Wv). The mice were pre-sensitized by application of 2% oxazolone to the shaved abdomen. On day 5, 1% oxazolone and vehicle were applied to both sides of right ear and left ear, respectively. Contact hypersensitivity was evaluated by ear thickness.
Cytokine expression in the tissue was analyzed by Real-Time PCR.
As a result, oxazolone failed to cause ear swelling in W/Wv and Fc epsilon RI beta-chain -/- mice. In addition, we showed that ear swelling is significantly reduced in the FFF-knock-in mice as compared with that of YYY- knock-in mice. Consistent with this result, infiltration of CD3^<+> T cells and eosinophils into the inflammation sites was severely reduced in FFF-knock-in mice. Furthermore, an experiment using real-time PCR demonstrated that expression of TNF-alpha mRNA is also decreased in the ear tissue of FFF-knock-in mice. Taken together, these results suggest that regulation of mast cell activation through Fc epsilon RI beta-chain is critical for development of contact hypersensitivity following cutaneous exposure of hapten.
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